Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab

被引：64

作者：

Tamura, Ryota ^{[1
]}

Tanaka, Toshihide ^{[2
]}

Ohara, Kentaro ^{[3
]}

Miyake, Keisuke ^{[4
]}

Morimoto, Yukina ^{[1
]}

Yamamoto, Yohei ^{[2
]}

Kanai, Ryuichi ^{[5
]}

Akasaki, Yasuharu ^{[6
]}

Murayama, Yuichi ^{[6
]}

Tamiya, Takashi ^{[4
]}

Yoshida, Kazunari ^{[1
]}

Sasaki, Hikaru ^{[1
]}

机构：

[1] Keio Univ, Dept Neurosurg, Sch Med, Tokyo, Japan

[2] Jikei Univ, Dept Neurosurg, Kashiwa Hosp, Chiba, Japan

[3] Keio Univ, Div Diagnost Pathol, Sch Med, Tokyo, Japan

[4] Kagawa Univ Hosp, Dept Neurosurg, Takamatsu, Kagawa, Japan

[5] Eiju Gen Hosp, Dept Neurosurg, Tokyo, Japan

[6] Jikei Univ Hosp, Dept Neurosurg, Tokyo, Japan

来源：

CANCER SCIENCE | 2019年 / 110卷 / 02期

基金：

日本学术振兴会;

关键词：

bevacizumab; PD-1; PD-L1; TAM; Treg; REGULATORY T-CELLS; ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; IMMUNE SUPPRESSION; LUNG-CANCER; OPEN-LABEL; HYPOXIA; ATEZOLIZUMAB; MACROPHAGES; PROGRESSION;

D O I：

10.1111/cas.13889

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post-Bev recurrent tumors from 9 patients were included. The expression of programmed cell death-1 (PD-1)/PD ligand-1 (PD-L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD-L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naive Bev group (P < .01 for each). The PD-1+ cells significantly decreased in the effective or refractory Bev group compared with the naive Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naive Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages significantly decreased in the effective or refractory Bev group compared with the naive Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post-Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long-term Bev therapy.

引用

页码：499 / 508

页数：10

共 44 条

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